Dyslipidemia, Hypertension, and Atherosclerosis PDF

8 DYSLIPIDEMIA Lipid Terminology Lipoproteins = soluble complex of lipid & protein found in body fluid = can be chylomicrons, VLDL, LDL or HDL Cholesterol = hydroxyl group, steroid nucleus & hydrocarbon tail = precursor to many compounds (bile acids & steroid hormones) = 2/3 of plasma cholesterol is...

8 DYSLIPIDEMIA Lipid Terminology Lipoproteins = soluble complex of lipid & protein found in body fluid = can be chylomicrons, VLDL, LDL or HDL Cholesterol = hydroxyl group, steroid nucleus & hydrocarbon tail = precursor to many compounds (bile acids & steroid hormones) = 2/3 of plasma cholesterol is esterified with fatty acids to form cholesterol esters Triglycerides = lipid made of glycerol molecule and 3 fatty acids = transported from intestine and liver in lipoprotein particles = plasma triglyceride levels rise after fatty meal and remain increased for several hours Fatty acids = Straight chain carbon compounds of varying length (esterified, non-esterified or free) Pathogenesis of Atherosclerosis Endothelial damage à LDL particles cross damaged endothelium à damaged endothelium attracts circulating monocytes à LDL particles in artery wall are oxidized and taken up by macrophages (foam cells) à collagen overlies foam cells à necrosis or apoptosis occurs à formation of poll of extracellular cholesterol trapped beneath fibrous cap à lesion advances across inner surface of artery à plaques obstruct blood flow (ischemia) or rupture (thrombus formation) Fatty acid terminology Saturated = fatty acids which contain maximum possible number of hydrogen atoms (no carboncarbon double bonds) = solid at room temp and generally from animal products Polyunsaturated = fatty acid with more than one carbon-carbon double bond = oils at room temp and generally from plants Trans-unsaturated fatty acids = Product of hydrogenation of fats to produce foodstuff with a longer shelf life = harmful in relation to CVD. Omega acids = unsaturated essential fatty acids e.g. Omega 3 & Omega 6 = precursors to some prostaglandins, thromboxane & leukotrienes Essential fatty acids = Need to be consumed in the diet as humans can’t synthesize them Primary Hypercholesterolemia Also called polygenic hypercholesterolemia Levels of cholesterol that put people at increased risk of CVD Cholesterol values show Gaussian distribution Familial hypercholesterolemia Commonest genetic disease in Europe = 1/300 & most common syndrome leading to premature CHD Clinical features = xanthomata, xanthelasma & corneal arcus Lab diagnosis = 1/25 with cholesterol >7 mmol/L have FH Dutch lipid clinic network >8 points = definite FH 6-8 ppints = probable FH 3-5 = possible FH 2 months = scar HYPERTENSION BP = Blood volume x Peripheral vascular resistance Pathophysiology of essential hypertension Environmental factors, genetic factors and alterations to vascular tone & structure lead to Impaired renal function Impaired activation of hormones that regulate renal excretion of salt & water Excessive activation of sympathetic nervous system Impaired renal pressure natriuresis BP >140/90mmHg Mortality Cerebrovascular hemorrhage Fatal cardiac arrhytmias Heart failure Aortic dissection Renal failure Organ damage increases with age, in African/Americans & people with co-morbidities Secondary Hypertension causes 5% of cases Primary hyperaldosteronism (Conn’s syndrome) Thyrotoxicosis Pregnancy (pre-eclampsia) Coarctation of aorta Drug-induced Renal parenchymal disease Reno-vascular hypertension due to renal artery stenosis Essential vs Malignant Common Slow progression Hyaline arteriosclerosis Muscular thickening of larger arteries 10 End organ damage Causes direct damage to large vessels and small vessel Secondary effect on heart, kidney, brain & eye Major risk factor for atherosclerosis Aorta = dissection Heart = LVH Kidney = hypertensive kidney disease (arterionephrosclerosis) CNs = cerebral hemorrhage, lacunar infarcts & hypertensive syndromes (multi-infarct dementia, Binswanger Encephalopathy & Cerebral SVD) Eye = retinal vascular disease Uncommon Sudden rise in BP with rapid progression Fibrinoid necrosis Myointimal proliferation of small vessels